The European Commission ( EC ) has approved Opdivo ( Nivolumab ) plus Yervoy ( Ipilimumab ) with two cycles of Platinum-based chemotherapy for the first-line treatment of adult patients with metastatic non-small cell lung cancer ( NSCLC ) whose tumors have no sensitizing epidermal growth factor receptor ( EGFR ) mutation or anaplastic lymphoma kinase ( ALK ) translocation.
The combination of Opdivo plus Yervoy with two cycles of chemotherapy is the first dual immunotherapy-based treatment option approved for patients in the European Union ( EU ) with this disease.
The EC’s decision is based on results from the phase 3 CheckMate -9LA trial, which met its primary endpoint of superior overall survival ( OS ), as well as secondary endpoints of progression-free survival ( PFS ) and overall response rate ( ORR ), for the combination of Nivolumab plus Ipilimumab, given concomitantly with two cycles of chemotherapy, versus chemotherapy alone.
An improvement in duration of response ( DoR ) was also observed.
The safety profile of Nivolumab plus Ipilimumab and two cycles of chemotherapy was reflective of the known safety profiles of the immunotherapy and chemotherapy components in first-line NSCLC.
In the CheckMate -9LA trial, an interim analysis with a minimum follow-up of 8.1 months for overall survival demonstrated:
Nivolumab plus Ipilimumab combined with two cycles of chemotherapy reduced the risk of death by 31% compared to chemotherapy alone [ hazard ratio ( HR ): 0.69; 96.71% confidence interval ( CI ): 0.55 to 0.87; p=0.0006 ];
Median progression-free survival with the combination was 6.8 months compared to 5.0 months with chemotherapy alone ( HR: 0.70; 97.48% CI: 0.57 to 0.86; p=0.0001 );
Overall response rate was significantly higher for Nivolumab plus Ipilimumab with two cycles of chemotherapy versus chemotherapy alone: 38% vs. 25% ( p=0.0003 );
A subsequent analysis, with a minimum follow-up of 12.7 months, has shown sustained improvements in overall survival compared to chemotherapy alone ( HR: 0.66; 95% CI: 0.55 to 0.80 ).
The majority of select adverse reactions observed in patients who received Nivolumab plus Ipilimumab with two cycles of chemotherapy were mild to moderate.
Grade 3 or 4 treatment-related adverse events occurred in 47% of patients.
The most frequent adverse reactions were fatigue ( 36% ), nausea ( 26% ), rash ( 25% ), diarrhea ( 20% ), pruritus ( 18% ), decreased appetite ( 16% ), hypothyroidism ( 15% ) and vomiting ( 13% ).
CheckMate -9LA is an open-label, multi-center, randomized trial evaluating Nivolumab ( 360 mg Q3W ) plus Ipilimumab ( 1 mg/kg Q6W ) combined with histology-based chemotherapy ( two cycles ) compared to chemotherapy alone ( up to four cycles followed by optional Pemetrexed maintenance therapy if eligible ) as a first-line treatment in patients with metastatic non-small cell lung cancer regardless of PD-L1 expression and histology.
Patients in the experimental arm ( n=361 ) were treated with dual immunotherapy for up to two years or until disease progression or unacceptable toxicity.
Patients in the control arm ( n=358 ) were treated with up to four cycles of chemotherapy and optional Pemetrexed maintenance ( if eligible ) until disease progression or unacceptable toxicity.
The primary endpoint of the trial was overall survival in the intent-to-treat ( ITT ) population. Secondary hierarchical endpoints included progression-free survival and overall response rate as assessed by blinded independent review committee.
Exploratory analyses from the study evaluated efficacy measures according to biomarkers. ( Xagena )
Souce: BMS, 2020